In recent years, there has been a frantic search for research, development, and application of innovative technologies in the use of mixtures of macromolecules with functional properties, capable of stabilizing and delivering bioactive principles. Mainly, because the physicochemical properties of the mono molecular systems are not sufficient to be used as carriers in the delivery of drugs, lipids, bioactive molecules, and minerals. Of all of the administration routes, the oral route has been the most used (90% of the administration), because it provides low cost formulation systems, does not cause pain to the consumer, and allows to supply the active principle to the consumer regardless of age. However, these systems present important challenges to overcome during their journey in the digestive tract related to the digestion and absorption of the bioactive principles, which have as main obstacles the physical, enzymatic, or immunological barriers.
In the particular case of macro minerals such as calcium, the main problem of absorption is physical. One of the main sources of calcium is tribasic calcium phosphate.
The FDA (Food and Drug Administration) authorizes tricalcium phosphate as an additive and appears on the positive list of additives as E-341 (iii). In the year 2013, Annex III of the European Commission Rules No. 1333/2008 of the European Parliament and of the Council was amended by introducing tricalcium phosphate (E 341 (iii)) as an additive in foodstuffs and anti-binder in nutritive foods for newborns, kids, and young people. This is found naturally in cow's milk. Despite the low rate of dissolution and solubility, it is used as a mineral supplement to fortify cereals and pasta. Also as an anti-binder agent, acidity regulator, source of calcium in the prevention and treatment of calcium deficiencies (osteoporosis prevention). It is part of the essential biological reactions of the human system (benefits related to the precipitation of intestinal bile salts, decrease in blood lipid and cholesterol levels). At the present, the delivery of dosages is in the form of suspensions highly insoluble, limiting their bioaccessibility. The solution to the problem of solubility and availability has not been easy; there is no viable alternative to deliver calcium ions efficiently. Despite this, the market estimate of solid oral doses has increased in recent years, mainly in the geriatric population. It is estimated that the market was valued at $570.6 million during 2011, with a forecast of $869.1 million by 2018. Of that projection, 9.6% belongs to the mineral market. This creates an important expectation using the methodology of stabilization of ionized calcium.
It has been achieved ionization and stabilization of a soluble calcium complex using the colloidal technology. With this concept, a wide range of products have been glimpsed that can be improved and taken to the consumer, ensuring rapid absorption of macronutrients and other bioactive compounds of a similar nature. The soluble calcium complex of the present invention has been formulated at the laboratory level using highly soluble natural fibers such as chitosan, mesquite gum, fructans, and inulin. Its stability during storage has been tested under acidic conditions at room temperature. This invention is based on generating and promoting the development of a new methodology for producing the soluble calcium complex.
In patent document WO2007069072A2, it describes a food supplement based on mineral salts obtained with anions of organic or inorganic acids and metal cations such as calcium, magnesium, zinc, iron, copper, manganese, sodium, potassium, nickel, or cobalt. The mineral salts are stabilized with amino acids and/or ammonium salts, stabilized between the cationic bonds and the dative covalent bonds. However, in order for the amino acids and the metal cations, such as calcium, to carry out their respective biological functions, once they are consumed in the food supplement, the dissociation of the compounds is required. Thus, in this system, high energy expenditure is required to dispose of free ions in an aqueous medium; for example the energy required for the release of calcium is greater than 20 KJ/mol.
In patent CN1391444B, the fortification of products such as water, juices, beverages and other liquid food products, added with salts of calcium and magnesium with lactic and citric acid metastable, and optionally stabilized with carbohydrates are described. The disclosed invention has application in the field of beverages as referred to in the document.
U.S. Pat. No. 9,023,398B describes a method for improving the solubility of poorly soluble substances such as tribasic calcium phosphate for application in the pharmaceutical, cosmetic, food and agricultural industries. But methods applied to improve solubility comprise reducing the particle size to 100 μm or less by mechanical methods. The reduction of particle size means increase of surface area and increases of contact with hydrophilic solutions; followed by physical coating using citric acid, citrate, phosphoric, or chondroidine sulfate to enhance solubility. However, the process for delivering calcium as a dietary supplement is not specified.
U.S. Pat. No. 7,994,155 B2 describes an accelerator product for mineral absorption. The accelerator product is based on a non-reducing tetrasaccharide composed of four glucose residues, cyclically bound via α-1,3 and α-1,6, cyclo {>6)-α-D-glucopyranosyl-(1>3)-α-D-glucopyranosyl-(1>6)-α-D-glucopyranosyl-(1>3)-α-Glucopyranosyl (1>}) and/or saccharides derived there from. But is a recommended product to be added in different amounts, among them 0.01 g/kg body weight per day, or preferably 0.5 g/kg body weight per day, or more preferably 1.0 g/kg body weight per day or more on a dry basis and administered in food, beverages, pro-drugs, or medicaments and therefore is a general purpose tetrasaccharide, which can be used in various formulations at the recommended concentrations and are not specific.
Thus, the main technological purpose has been the development of complex intermolecular systems, used as carriers capable of stabilizing and delivering bioactive compounds with multiple applications. Especially because the properties of the mono-molecular components are not sufficient to overcome the effects of the different process conditions or stability.
Fundamentally, because all those products that have the purpose of nourishing do not achieve the solvation process of multiple nutrient molecules. A challenge that must be overcome, since 90% of the routes of administration are oral.
Accordingly, a primary object of the present invention is to stabilize insoluble calcium salts in aqueous solutions and to administer them as a food supplement or in food, pharmaceutical, or cosmetic products.